Download I PHYTOTHERAPY IN THE TREATMENT OF BENIGN PROSTATIC HYPERPLASIA: AN UPDATE

CLINICAL REVIEW
PHYTOTHERAPY IN THE TREATMENT OF BENIGN
PROSTATIC HYPERPLASIA: AN UPDATE
FRANKLIN C. LOWE
I
t has been almost 3 years since the previous review of phytotherapeutic agents for benign prostatic hyperplasia (BPH) by Lowe appeared in Urology.1 During this period, there has been a rapid
increase in the use of these products in the United
States as well as substantial widespread use in Europe. It has been estimated that total sales of medicinal botanicals in the United States has risen
from more than $500,000 to approximately $1 billion during this time.1–3
In the urology practice of one of us (F.C.L.),
more than 90% of the newly referred patients with
lower urinary tract symptoms (LUTS) secondary to
BPH have already tried or are using some form of
alternative/complementary medications.4 The
most commonly used agents are saw palmetto
berry (SPB) extract, “men’s health pills” (which
contain multiple botanicals), zinc, selenium, and
vitamin E. A recent national survey conducted by
National Family Opinion Inc. and reported in
JAMA determined that the widespread use of these
agents was due to philosophical congruence with
peoples’ own values, beliefs, and orientation toward health and life.5
In fact, the younger, better educated, healthier
people tended to be the greatest users of complementary medications.5 Therefore, it is not surprising that many of these medicinal botanicals/phytotherapeutic agents are being sold over the Internet.
Last year, more than 100 websites marketing SPB
or some other formulation of “men’s health” or
“prostate health” pills containing SPB were identified.4
Despite the increased use of these agents in the
United States, most American urologists have little
knowledge or understanding of them. In fact, most
American physicians are very skeptical about the
use of phytotherapeutic agents because of the limFrom the Department of Urology, St. Luke’s Roosevelt Hospital
Center and Columbia University, College of Physicians and Surgeons, New York, New York
Reprint requests: Franklin C. Lowe, M.D., 425 West 59th
Street, 3A, New York, NY 10019
Submitted: October 28, 1998, accepted (with revisions): December 7, 1998
© 1999, ELSEVIER SCIENCE INC.
ALL RIGHTS RESERVED
AND
ELLIOT FAGELMAN
ited evidence of their efficacy.6 However, over the
past 3 years numerous studies assessing the efficacy and determining the mechanism of action of
these agents have been published.3 These reports
are critically evaluated herein.
COMPARABILITY OF PLANT EXTRACTS
Numerous plant extracts have been used in the
treatment of LUTS secondary to BPH (Table I).
Some of these extracts are derived from the roots,
seeds, bark, or fruits of the plants shown in Table I.
These phytotherapeutic agents are available as either a single agent (monopreparation) or more
likely as a combination product. This variation obviously makes comparisons between products difficult.
Additionally, plant extracts are composed of numerous components (Table II). The extracts are
synthesized by different extraction procedures.
Therefore, the botanical product of one company
may be different from that of another with regard
to specific composition and effective components
(because we do not know what the active components of these products are), even if they originate
from the same plant.3 There is also natural variability among the plants themselves.
Because the results of basic research and clinical
trials cannot be automatically accepted and/or
transferred from one new manufacturer’s product
to another, the different preparations from each
individual manufacturer need to be evaluated individually. This necessity was emphasized by the
Committee on Other Medical Therapies of the
Fourth International Consultation on Benign Prostatic Hyperplasia.3
SERENOA REPENS
(SAW PALMETTO BERRY EXTRACT)
SPB extract remains the most popular and widely
used phytotherapeutic agent for LUTS secondary
to BPH. Two extensive reviews of this agent have
been published since our last review in this journal.7,8
UROLOGY 53: 671– 678, 1999•0090-4295/99/$20.00
PII S0090-4295(98)00664-5 671
TABLE I. Origin of plant extracts used in
treatment of benign prostatic hyperplasia
Vernacular Name
African plum
Purple cone flower
Pumpkin seeds
Rye
Saw palmetto berry/
dwarf palm
South African star grass
Stinging nettle
Scientific Name
Pygeum africanum
Echinacea purpurea
Cucurbita pepo
Secale cereale
Serenoa repens
Hipoxis rooperi
Urtica dioica
Adapted with permission of Elsevier Science from Urology, 48, F. C. Lowe and J. C.
Ku, Phytotherapy in treatment of benign prostatic hyperplasia: a critical review,
12–20, 1996.
TABLE II.
Some of the components of plant
extracts*
Phytosterols
Phytoestrogens
Terpenoids
Fatty acids
Lectins
Plant oils
Polysaccharides
Flavonoids
* Data from Dreikorn et al.3
MECHANISM OF ACTION
Most in vitro studies that have sought to elucidate the mechanisms of action of SPB extract have
been performed using Permixon, the liposterolic
extract of SPB. In recent publications, it has been
postulated that the liposterolic extract of Serenoa
repens has antiandrogenic effects,9 inhibits the type
1 and type 2 isoenzymes of 5-alpha-reductase,10 –12
inhibits prolactin and growth factor-induced cell
proliferation,13,14 and has antiestrogenic15 and anti-inflammatory16 effects.
However, most of these in vitro studies were performed in cell cultures or used supraphysiologic
dosages of SPB extract. Therefore, the significance
of these mechanism studies is uncertain.
Di Silverio et al.,17 in a recent ex vivo study, supported the concept that the liposterolic extract of
SPB (Permixon) has antiandrogenic effects that inhibit the type 1 and type 2 isoenzymes of 5-alphareductase. In a randomized study, 33 patients with
BPH underwent suprapubic transvesical prostatectomy after being treated with either finasteride (5
mg/day for 3 months), flutamide (750 mg/day for 2
months) or Permixon (320 mg/day for 3 months)
or received no treatment. None of these treatments
caused a significant alteration in tissue concentrations of testosterone. However, both Permixon and
finasteride exhibited a 50% reduction in prostate
dihydrotestosterone (DHT) levels (P ,0.01)
compared with flutamide or with no treatment. For
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both agents, this effect was primarily in the periurethral zone tissues.
In contrast, Weisser et al.18 performed a prospective, randomized, double-blind trial using an extract of Sabal serrulata (IDS-89) to determine the
possible influence on epithelial and stromal enzymes in BPH tissue. Patients were treated with
either placebo or IDS-89 for 3 months, at which
time they underwent suprapubic transvesical prostatectomy. The tissues were evaluated for 5-alphareductase,
3-alphaand
3-beta-hydroxysteroid oxidoreductase, and creatine kinase activity. There was no difference in 5-alpha-reductase
and 3-alpha- and 3-beta-hydroxysteroid activity
between those treated with IDS-89 versus placebo.
However, creatine kinase activity was statistically
significantly increased in patients treated with IDS89. Because the synthesis of creatine kinase is estrogen dependent, it is possible that IDS-89 might
affect the balance of androgens in relation to estrogens. The clinical significance of this possibility is
not known.
Between-group pathologic comparisons of the
tissue were also analyzed and reported separately.19 Those pretreated with S. serralata showed a
significant reduction in periglandular and stromal
edema, mucoid degeneration, intraglandular congestion, and “congestive prostatitis.” The clinical
significance of these pathologic findings is unclear.
In contrast, previous laboratory studies by
Rhodes et al.20 did not demonstrate any inhibition
of DHT binding to rat prostatic androgen receptor
or inhibition of DHT activity. Additionally, several
clinical studies measured serum testosterone,
DHT, prostate-specific antigen (PSA), and folliclestimulating hormone (FSH) levels in patients given
SPB extracts for variable periods of time up to 6
months.20 –24 None of these studies showed any alteration in testosterone, DHT, PSA, and FSH levels.
Therefore, the effect on hormone metabolism and
5-alpha-reductase activity by S. repens (including
Permixon) has yet to be determined conclusively.
CLINICAL STUDIES
Since our previous review, another placebo-controlled study has been published in which 176 of
215 nonreponders to placebo were randomized to
receive Permixon 160 mg twice daily or placebo for
30 days.25 Subsequent evaluation showed that dysuria, daytime frequency, nocturia, and peak urinary flows were all improved in Permixon-treated
patients compared with baseline values and placebo-treated patients (Table III). However, at the end
of the study, when the patients and physicians
were asked to assess global efficacy of the different
treatments, there was no statistical difference in
satisfactory responses between Permixon therapy
(71% and 57%) and placebo treatment (68% and
UROLOGY 53 (4), 1999
TABLE III. Comparison of Permixon and
placebo for benign prostatic hyperplasia*
Placebo
Mean change in daytime
frequency episodes
% change
Mean change in nocturia
episodes
% change
Mean change in Qmax
Absolute change
% change
Patient global efficacy
Physician global efficacy
TABLE IV. Outcomes of therapy after 26
weeks with Permixon or finasteride (Proscar)*
Permixon P Value
20.2%
20.8
0.012
22.9%
20.3
211.3%
20.7
0.028
217.7%
232.5%
11.1
18.5%
67.5%
47.2%
13.4
128.9%
71.3%
56.6%
0.038
NS
NS
IPSS
Absolute change
% change
Qmax (mL/s)
Absolute change
% change
Quality of life
Absolute change
% change
Permixon
Proscar
25.8
237%
26.2
239%
2.7
125%
3.2
130%
21.4
238%
21.5
241%
KEY: IPSS 5 International Prostate Symptom Score; Qmax 5 maximal urinary flow.
* Data from Casarosa et al.21
KEY: Qmax 5 maximal urinary flow; NS 5 not significant.
* Data from Descotes et al.25
47%), respectively. Thus, this “positive” study of
Permixon therapy did not show any actual perceived clinical benefit by the patients or their physicians.
Because conclusive clinical trial data do not exist
with regard to the efficacy of SPB extract in treating
BPH, a meta-analysis of all the clinical trials of Permixon therapy was undertaken.26 Using state of
the art statistical methodology, 12 Permixon trials
involving 2794 men (1929 receiving Permixon)
were evaluated for the available information regarding peak urinary flow rate and nocturia. Because these studies were performed before the advent of the American Urological Association
Symptom Index and the International Prostate
Symptom Score (IPSS), only the symptom results
for nocturia were available in all 12 studies.
Over all the trials, the placebo effect was seen as
an average increase in peak flow (Qmax) of 0.94
mL/s (standard error [SE] 0.49). The estimated effect of Permixon therapy relative to placebo was a
further increase of 1.87 mL/s (SE 0.55, P ,0.001).
The frequency of nocturia was decreased by an average of 0.65 (SE 0.17) for placebo. Permixon therapy further reduced nocturia by 0.55 (SE 0.1, P
,0.001).
The conclusions of this meta-analysis must be
tempered by the fact that most of the studies were
small (eight had fewer than 100 patients) and of
short duration (none longer than 6 months) and
lacked standardized symptom scores. However,
publication bias was avoided by including all the
studies. The number of studies included and the
total aggregate sample size were large, and state of
the art statistical methodology was used.
COMPARATIVE TRIAL
The most frequently referenced and discussed
trial concerning SPB extract (Permixon) was the
comparative trial with finasteride.27 This 6-month,
UROLOGY 53 (4), 1999
double-blind, randomized trial of 1098 patients
was conducted to demonstrate that the efficacy of
Permixon was equivalent to finasteride (Proscar)
(Table IV).
Both Permixon and finasteride decreased the total IPSS by a similar extent: 237% and 239%, respectively (approximately six points). Peak flow
increased by 3.2 mL/s in the finasteride group compared with 2.7 mL/s in the Permixon group. These
differences were statistically significant (P ,0.01)
compared with baseline values. There was also a
statistically significant decrease in residual urine in
the finasteride group. PSA levels were unchanged
in the Permixon group and fell in the finasteride
group by 41%. Prostate size decreased more in the
finasteride group than in the Permixon group (by
18% versus 6%).
This well-designed and well-executed trial supports the equivalency of Permixon to finasteride in
treating men with moderate to severe symptoms of
BPH, with less decrease in sexual function. However, the lack of a placebo group clouds the efficacy
issue.6,7 With the study being only 6 months in
duration, it is possible that the effect is due to the
placebo effect, which will eventually fade with
time.28 Additionally, the study by Lepor et al.29 indicated that finasteride was not statistically better
than placebo. Therefore, comparing Permixon
with finasteride might simply be showing equivalency to placebo.6,7
URODYNAMIC EFFECTS
In a 6-month, open-label study utilizing SPB extract (Nutraceutical Corp, Ogden, Utah), 50 men
were evaluated urodynamically at baseline and at
completion of the study.24 The IPSS (mean 6 standard deviation) improved from 19.5 6 5.5 to
12.5 6 7.0 (P ,0.001). Although a greater than
50% improvement in IPSS was identified in 21%,
30%, and 46% of patients at 2, 4, and 6 months,
respectively, no demonstrable changes in peak uri673
nary flow rate, postvoid residual volume, or detrusor pressure at peak flow were found. This study
demonstrated no correlation between relief of urodynamic signs of obstruction and a decrease in
LUTS. Without an appropriate control arm, the
attributable drug effect of SPB extract cannot be
demonstrated.30 Thus, the effect may be largely attributable to the placebo effect.24
SUMMARY OF CLINICAL TRIALS OF S. REPENS
Obviously, all the uncontrolled and comparative
trials utilizing SPB extract without placebo control
arms are not useful in defining the efficacy of this
product in the treatment of BPH. The randomized,
placebo-controlled studies are hampered by short
duration, variable inclusion/exclusion criteria, and
lack of uniform symptom score analysis.1 The
meta-analysis of Permixon suggests clinical efficacy for this product26; however, the analysis was
performed using supoptimal studies. Although Descotes et al.25 demonstrated that patients could
have statistically significant improvements in nocturia and peak urinary flow with Permixon therapy, patient and physician global assessments of
efficacy were no different between Permixon and
placebo.25
Despite its being the most widely evaluated phytotherapeutic agent, the efficacy of SPB extract
therapy in the treatment of LUTS secondary to BPH
has yet to be conclusively determined. Appropriate
long-term, placebo-controlled trials are still
needed for each individual manufacturer’s product
to ascertain its true efficacy.
PYGEUM AFRICANUM (AFRICAN PLUM)
Pygeum africanum extract (Tadenan) comes from
the bark of the African plum tree and is widely used
in France and throughout Europe. Other formulations (Prostata and numerous others) are available
in health food and nutrition shops throughout the
United States. Almost all the research and clinical
trials of this product have been done using the
product Tadenan.
MECHANISM OF ACTION
In vitro data indicate that the Tadenan extract
has several effects: inhibition of b-fibroblast
growth factor- and epidermal growth factor-induced fibroblast proliferation,31–33 inhibition of
production of chemotactic leukotrienes and other
5-lipoxygenase metabolites (anti-inflammatory effect),34 and antiestrogenic effects.35
Recent studies by Levin et al.36,37 suggest that the
effects of P. africanum (Tandenan) on LUTS might
be mediated through alterations in bladder function. Using a rabbit model with partial bladder outlet obstruction (a model for bladder dysfunction
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secondary to BPH), Levin et al.36 demonstrated that
changes in bladder mass, decrease in compliance,
and alterations in contractile response to various
forms of stimulation could be protected and tempered by Tadenan pretreatment.
In a second study, after 2 weeks of bladder obstruction in a rabbit model, treatment with Tadenan (100 mg/kg body weight) reversed both contractile dysfunction and compliance changes that
were previously identified.37 However, doses of up
to 100 mg/kg body weight are highly supraphysiologic; the recommended daily dose in humans is
only 100 mg. Therefore, the applicability of this
findings to humans is uncertain.
CLINICAL STUDIES
A review of the published experience with P. africanum (Tadenan) identified 2262 patients treated
with this extract: 1810 patients in open-label studies and 452 in comparative trials.38 Twelve doubleblind, placebo-controlled studies were completed
between 1972 and 1990. Only one study had more
than 100 patients, and none were longer than 12
weeks. None of those trials meet the guidelines
recommended by the International Consultation
Conferences on BPH; thus, the data concerning the
efficacy of P. africanum are not conclusive.
In December 1996, the Tadenant-IPSS trial, a
double-blind, placebo-controlled trial comparing
Tadenan 100-mg and 400-mg daily dosage with
placebo was commenced in Europe; 750 men were
to be randomized. The trial should be completed
by December 1998, with data available in 1999. It
is hoped that this trial will provide some conclusive data on the efficacy of this agent.
UNCONTROLLED CLINICAL STUDIES
Breza et al.39 recently completed a 2-month
open-label trial utilizing a 100-mg daily dosage of
P. africanum (Tadenan). The IPSS was 16.17 6
3.68 at baseline and 9.71 6 4.57 at the end of
treatment; this 40% reduction in symptom scores
was statistically significant (P ,0.0125). Mean
peak urinary flow rates were 10.97 6 3.58 mL/s at
baseline and 13.07 6 5.56 mL/s at the end of therapy (P ,0.001). No side effects were identified in
the study group. Obviously, this uncontrolled
study only suggests a benefit of this agent. No further conclusions can be made from this study.
COMPARATIVE TRIAL
Abbou et al.40 compared alfusosin, an alpha1A
selective agent, with an extract of P. africanum; 331
men completed this 8-week trial. Alfusosin was
found to be more effective than P. africanum with
regard to peak flow rate, decrease in residual urine,
and decrease in irritative symptoms. This non-placebo-controlled study unfortunately adds little to
UROLOGY 53 (4), 1999
our knowledge of the efficacy of P. africanum but is
presented for completeness.
URODYNAMIC EFFECTS
In a recent review of the baseline and post-treatment uroflow tracings from 20 patients treated
with 100 mg of Tandenan daily for 2 months,41 7
patients were deemed “greatly improved,” and 5
were deemed “slightly improved.” True pressureflow evaluations were not completed; therefore,
these uroflowmetry data, which were analyzed by
mathematical modeling, add little useful information regarding the effect of P. africanum on bladder
function and outlet obstruction.
SUMMARY OF P. AFRICANUM
Until the Tadenan-IPSS study is completed, the
available data concerning the efficacy of P. africanum in treating LUTS secondary to BPH are lacking. There is a large pool of suboptimal data concerning Tadenan use; however, there are few
significant data available with regard to any of the
other P. africanum extracts.
URTICA DIOICA (STINGING NETTLE)
Extracts from the roots of a stinging nettle are
widely used in Germany.3 The extracts of the roots
of the stinging nettle contain a complex mixture of
water- and alcohol-soluble compounds. It is clear
that the extraction procedures significantly vary
from company to company.
MECHANISM OF ACTION
There have been three recent studies that suggest
different mechanisms of action for stinging nettle.
These include inhibition of prostatic growth factor
interaction,42 inhibition of membrane sodium and
potassium-adenosine triphosphatase in the prostate, with resulting suppression of prostate cell metabolism and growth,43 and modulation of binding
of sex hormone-binding globulin to its receptor on
prostate cell membranes.44 These laboratory studies only suggest possible mechanisms of action.
CLINICAL STUDIES
The only recent study with a stinging nettle extract used a liquid preparation.45 The liquid preparation has subsequently been removed from the
market because its unacceptable taste was rejected
by patients.3 In that study, 41 patients were randomized to receive either placebo or the stinging
nettle preparation. They were treated for a period
of 3 months. Treated patients had superior improvement compared with placebo recipients in
terms of IPSS results.45
UROLOGY 53 (4), 1999
TABLE V.
Prostaglutt forte versus placebo*
IPSS
Baseline
Week 24†
Week 48‡
Qmax (mL/s)
Treated
Placebo
Treated
Placebo
18.6
11.1
9.8
19.0
17.6
13.3
14.65
17.95
19.10
15.05
15.50
17.50
KEY: Abbreviations as in Tables III and IV.
* Data from Metzker and Martin.46
†
End of double-blind period.
‡
End of open extension.
SUMMARY OF U. DIOICA
This agent has been studied less extensively than
either S. repens or P. africanum. The data to date
available do not confirm its efficacy in the treatment of LUTS secondary to BPH.
CLINICAL TRIALS WITH COMBINATION
PRODUCTS
Although there are no data to suggest either increased efficacy or synergy by combining plant extracts, most “prostate health” pills are combinations. Two studies of the preparation Prostagutt
forte (combination of S. repens and U. dioica) were
recently reported.46,47 The randomized, placebocontrolled study included only 20 patients in each
arm.47 After a 2-week placebo lead-in period, there
was 6 months of double-blind treatment, followed
by 6 months of open-label treatment (Table V). In
that study, both IPSS and peak flow rate showed
greater improvement with treatment than with placebo. The IPSS went from 18.6 down to 11.1 with
Prostaglutt and from 19 to 17.6 with placebo (P 5
0.002). During the open-label extension phase,
the placebo group improved from 17.6 to 13.3;
surprisingly, the Prostaglutt-treated group also
continued to improve, dropping from 11.1 to 9.8.
In terms of peak flow rates, the Prostaglutt-treated
patients improved by 2.3 mL/s over the first 6
months and by an additional 1.15 mL/s over the
open-label second 6-month period. The placebo
group showed minimal change during the initial
placebo period (0.45 mL/s); however, during active treatment there was a 2-mL/s improvement.
Thus, this study indicated that further improvement with Prostaglutt therapy can be achieved
with longer treatment (from 6 to 12 months). This
finding further supports the need for double-blind,
placebo-controlled studies of at least 1 year in duration to evaluate plant extract therapy.
COMPARATIVE TRIAL
Prostaglutt forte was also compared with finasteride (Proscar) in a comparative trial that did not
have a placebo control arm48; 489 patients were
randomized and followed up for 48 weeks. The
675
IPSS improved from 11.3 to 6.5 for Prostaglutttreated patients and from 12.6 to 6.9 in finasteridetreated patients. Although the improvement was
slightly greater in the finasteride-treated patients
(5.7 versus 4.8), there was no statistical significance between the treatment groups. In terms of
improvement in peak urinary flow, Prostaglutttreated patients improved by 1.9 mL/s and finasteride-treated patients by 2.7 mL/s (P 5 0.189),
also not statistically significant between groups.
The significance of this study is obviously questionable without a placebo control arm.
SECALE CEREALE (RYE POLLEN)
The rye pollen extract is obtained by microbial
digestion of the pollen, followed by extraction with
both water and organic solvents. Thus, the total
extract consists of both a water-soluble and a fatsoluble fraction. Habib et al.49 studied the watersoluble fraction and found that it inhibited the
growth of immortal prostate cancer cell lines as
well as epithelial and stromal cells derived from
BPH tissue in cell culture. Whether this in vitro
action also occurs in vivo is uncertain.
CLINICAL TRIALS
No new double-blind, placebo-controlled trials
have been performed since our previous review.
There was one comparative trial between Cernilton (rye pollen) and Tadenan (P. africanum),
which did not have a placebo control arm. This
4-month study with 89 patients suggested that
Cernilton provided better improvement in symptom score, peak flow, and residual urinary volume
than Tadenan.50 The significance of this study is
also inconclusive.
SUMMARY OF S. CEREALE
Further long-term, double-blind, placebo-controlled trials need to be performed to determine the
efficacy of rye pollen extracts.
HYPOXIS ROOPERI (SOUTH AFRICAN STAR
GRASS)
This extract mainly contains beta-sitosterol
(Harzol), along with various amounts of several
other sterols. Beta-sitosterol is thought to be a major active component in plant extracts.
MECHANISM OF ACTION
In laboratory studies, Harzol was found to enhance the production and secretion of plasminogen activators in isolated and epithelial cells. Additionally, prostate stromal cell cultures when
conditioned with beta-sitosterol were found to
have elevated levels of transforming growth factor
(TGF)-beta1. TGF-beta1 is an important differenti676
ation factor and apoptosis inducer.51 None of these
effects have been shown to occur in vivo or to be
clinically relevant.
CLINICAL TRIALS
Harzol was previously evaluated in a 6-month,
double-blind, placebo-controlled study.52 Statistically significant improvements were noted for
IPSS, quality of life, peak flow rates, and residual
urinary volumes. The placebo group showed an
appropriate mild improvement in these variables.
The IPSS improved by 2.3 for placebo and 7.4 for
beta-sitosterol–treated patients.52 Similarly, peak
urinary flow rates improved by 1.1 mL/s for placebo recipients and by 5.2 mL/s for treated patients. The magnitude of this improvement in flow
rates had not been observed with any other medical
therapy previously evaluated for BPH. This study
was favorably evaluated by reviewers.1
At the Fourth International Consultation on BPH
in Paris in 1997, Senge reported on the 18-month
follow-up data for these aforementioned patients.3
In patients who continued to receive Harzol, IPSS
improvements were maintained. Placebo recipients who were then treated with Harzol also demonstrated similar levels of improvement in IPSS
and flow rate. Most surprisingly, patients who were
initially treated with Harzol but then received placebo over the next 12 months still maintained similar levels of improvement. This finding suggests
the possibility that intermittent therapy might be a
viable option. We await final publication of this
study to evaluate it critically.
Another agent containing mainly beta-sitosterol
(Azuprostat) was evaluated in a 6-month randomized, placebo-controlled trial.53 Treated patients
received 65 mg twice daily during the 6 months of
treatment. Significant improvements in IPSS, urinary flow rates, and postvoid residual volumes
were noted. The IPSS improved by 2.8 for placebotreated patients and by 8.2 for beta-sitosterol–
treated patients. Peak flow rates improved by 4.4
mL/s for placebo recipients and by 8.8 mL/s for
treated patients. Therefore, the attributable drug
effect was 4.5 mL/s. The magnitude of improvement of 8.8 mL/s with beta-sitosterol in treated
patients in this study is dramatic and has not been
previously reported for any medical therapy for
BPH. If these results are reproducible, they would
rival those of surgical intervention.
SUMMARY OF BETA-SITOSTEROL
The aforementioned trials by Berges et al.52 and
Klippel et al.53 are exciting. They were performed
according to the recommendations of the International Consultations on BPH. The results of the
studies are certainly dramatic. We await confirmaUROLOGY 53 (4), 1999
tory studies to ascertain whether this magnitude of
improvement can be duplicated.
COMMENT
In the present review, the recent laboratory and
clinical trials using phytotherapeutic agents were
evaluated. Two other recent articles have reviewed
aspects of this topic.54,55 Such critical appraisal and
review of the topic reconfirms that appropriate
long-term, placebo-controlled, double-blind clinical trials using these phytotherapeutic agents are
still needed. Although several studies suggest the
clinical efficacy of certain agents, confirmatory
studies with these specific products are still
needed. Clearly, the widespread use of phytotherapeutic products necessitates our ascertaining the
true magnitude and level of efficacy of these products. Continued laboratory analysis is also required to determine the active ingredient or ingredients and their mechanism of action.
Overall, the efficacy of phytotherapeutic agents
for BPH has yet to be determined; however, preliminary trials suggest a benefit for this type of therapy.
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